Sodium Bicarbonate → (R)-methyl 2-((2-chloro-5-nitropyrimidin-4-yl)(isopropyl)amino)butanoate

Temperature

80 °C

2,4-Dichloro-5-nitro-pyrimidine (19.90 g, 103 mmol) was dissolved in 300 mL of cyclohexane followed by the addition of methyl (2R)-2-(isopropylamino)butanoate 22a (16.40 g, 103 mmol) and sodium bicarbonate (36.61 g, 412 mmol). The reaction solution was heated to 80° C., stirred for 4 hours and filtered. The filtrate was concentrated under reduced pressure, added with 100 mL of water and extracted with dichloromethane (100 mL×3). The combined organic phase was washed with saturated sodium chloride solution (100 mL), then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound methyl (2R)-2-[(2-chloro-5-nitro-pyrimidin-4-yl)-isopropyl-amino]butanoate 22b (20.50 g, yield: 62.8%) as a yellow solid.

1. filtrationfiltered
2. concentrationThe filtrate was concentrated under reduced pressure
3. additionadded with 100 mL of water
4. extractionextracted with dichloromethane (100 mL×3)
5. washThe combined organic phase was washed with saturated sodium chloride solution (100 mL)
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationfiltered
8. concentrationthe filtrate was concentrated under reduced pressure
9. customThe resulting residue was purified by silica gel column chromatography

ORD record

ord-6244ab19238a41828486b17f6368d05a

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691822B2